Compensatory T Cell Responses in IRG-Deficient Mice Prevent Sustained Chlamydia trachomatis Infections

PLoS Pathogens

Andrew J. Olive¹  Dave C. Gondek¹  Amy Rohlfing¹  Jörn Coers²  Gregory A. Taylor³  Michael N. Starnbach⁴ 

[1] Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America;Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America;Departments of Medicine, Molecular Genetics and Microbiology, and Immunology and Center for the Study of Aging, Duke University, Durham, North Carolina, United States of America;Geriatric Research and Education and Clinical Center, Veteran Affairs Medical Center, Durham, North Carolina, United States of America

关键词: Chlamydia trachomatis;    T cells;    Chlamydia infection;    Uterus;    Mouse models;    Immune response;    Sexually transmitted diseases;    Tryptophan;   

DOI  :  10.1371/journal.ppat.1001346

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The obligate intracellular pathogen Chlamydia trachomatis is the most common cause of bacterial sexually transmitted diseases in the United States. In women C. trachomatis can establish persistent genital infections that lead to pelvic inflammatory disease and sterility. In contrast to natural infections in humans, experimentally induced infections with C. trachomatis in mice are rapidly cleared. The cytokine interferon-γ (IFNγ) plays a critical role in the clearance of C. trachomatis infections in mice. Because IFNγ induces an antimicrobial defense system in mice but not in humans that is composed of a large family of Immunity Related GTPases (IRGs), we questioned whether mice deficient in IRG immunity would develop persistent infections with C. trachomatis as observed in human patients. We found that IRG-deficient Irgm1/m3(-/-) mice transiently develop high bacterial burden post intrauterine infection, but subsequently clear the infection more efficiently than wildtype mice. We show that the delayed but highly effective clearance of intrauterine C. trachomatis infections in Irgm1/m3(-/-) mice is dependent on an exacerbated CD4+ T cell response. These findings indicate that the absence of the predominant murine innate effector mechanism restricting C. trachomatis growth inside epithelial cells results in a compensatory adaptive immune response, which is at least in part driven by CD4+ T cells and prevents the establishment of a persistent infection in mice.

【 授权许可】

CC BY